The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
A Role for iNOS in Fasting Hyperglycemia and Impaired Insulin Signaling in the Liver of Obese Diabetic Mice
Open accessAbstract
Chronic inflammation has been postulated to play an important role in the pathogenesis of insulin resistance. Inducible nitric oxide synthase (iNOS) has been implicated in many human diseases associated with inflammation. iNOS deficiency was shown to prevent high-fat diet-induced insulin resistance in skeletal muscle but not in the liver. A role for iNOS in fasting hyperglycemia and hepatic insulin resistance, however, remains to be investigated in obesity-related diabetes. To address this issue, we examined the effects of a specific inhibitor for iNOS, L-NIL, in obese diabetic (ob/ob) mice. iNOS expression was increased in the liver of ob/ob mice compared with wild-type mice. Treatment with iNOS inhibitor reversed fasting hyperglycemia with concomitant amelioration of hyperinsulinemia and improved insulin sensitivity in ob/ob mice. iNOS inhibitor also increased the protein expression of insulin receptor substrate (IRS)-1 and -2 1.5- and 2-fold, respectively, and enhanced IRS-1- and IRS-2-mediated insulin signaling in the liver of ob/ob mice. Exposure to NO donor and ectopically expressed iNOS decreased the protein expression of IRS-1 and -2 in cultured hepatocytes. These results suggest that iNOS plays a role in fasting hyperglycemia and contributes to hepatic insulin resistance in ob/ob mice.
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“and the use of an NOS2-specific inhibitor (L-NIL) reversed hyperglycemia, hyperinsulinemia, and insulin resistance in ob/ob mice [150].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [150]
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Cites
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“Inducible nitric oxide synthase (iNOS; also termed NOS2), whose expression is regulated by IKK –NF- B (6), is assumed to be one of the candidates that mediate inflammation-involved insulin resistance.”
Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.-W., Karin, M., & Shoelson, S. E. (2001) · Science · doi:10.1126/science.1061620 · Cited by 1,884
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Potential Role of TNF-α in the Pathogenesis of Insulin Resistance and Type 2 Diabetes
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New Perspectives into the Molecular Pathogenesis and Treatment of Type 2 Diabetes
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Items 201–208 of 208
Low Hepatic CEACAM1 Tethers Metabolic Dysfunction Steatohepatitis to Atherosclerosis
Khoury, S. E., Harake, S. N. A., Youssef, T., Risk, C. E., Helou, N., Doumet, N. M., Aramouni, K., Azar, S. T., Najjar, S. M., & Ghadieh, H. E. (2025) · Livers · doi:10.3390/livers5030034
“Abnormal eNOS activity was reported in insulin resistance, leading to low NO production [231,232].”
Hemodynamic and metabolic actions of Adiponectin in muscle
Bussey, C. T. (2011) · UTAS Research Repository · doi:10.25959/23211008
Fasting Hypoglycemia and Preserved Renal Function in Endothelial NO Synthase Knockout Mice
Kutina, A. V., Belyakov, G. V., Balbotkina, E. V., Vishnyakova, P., Kosyreva, A. M., Chirinskaite, A. V., Sopova, J. V., & Leonova, E. I. (2025) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093025050187
“Various and often opposite changes in carbohy(cid:2) drate and lipid metabolism were described in a num(cid:2) ber of studies on mice with various nitric oxide synthase defects [3, 5, 18, 28].”
Emerging role of protein S-nitrosylation in diabetes and diabetes-associated diseases
Yu, M., He, J., Xu, M., 张真稳, Shang, W., & Fang, P. (2026) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2026.110823
Zanotto, T. M., Santos, A., Vecina, J. F., Quaresma, P. G. F., Guadagnini, D., Rocha, G. Z., Brambilla, S. R., Carvalho, C. R. D. O., & Saad, M. J. A. (2026) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2026.112875
Papel de la disfunción endotelial en pacientes con hepatopatía crónica e hipertensión portal
Cossio-Pérez, B. J., Traconis, A. P. M., & Barbero-Becerra, V. J. (2026) · Hepatología · doi:10.59093/27112330.174
Pasarín, M. (2012) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Metadata
- Authors
- Fujimoto, M., Shimizu, N., Kunii, K., Martyn, J. A. J., Ueki, K., & Kaneki, M.
- Affiliations
- Harvard University (US)
- The University of Tokyo (JP)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-05-01
- Volume
- 54
- Issue
- 5
- Pages
- 1340-1348
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2138266804
- Cited by
- 209
- References
- 47
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 15 · 2018: 12 · 2017: 10 · 2016: 10 · 2015: 24 · 2014: 14 · 2013: 7 · 2012: 15
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Shriners Hospitals for Children
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM055082, R01GM031569, R01GM061411)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058127)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- inducible nitric oxide synthase, fasting hyperglycemia, hepatic insulin resistance, insulin signaling, IRS-1, insulin receptor substrate 2, L-NIL, ob/ob mice, obesity, type 2 diabetes, nitric oxide, chronic inflammation, hepatocytes
- MeSH terms
- Animals, Cells, Cultured, Diabetes Mellitus, Type 2, Enzyme Inhibitors, Fasting, Hyperglycemia, Insulin, Insulin Resistance, Liver, Lysine, Male, Mice, Obese, Signal Transduction, Nitric Oxide Synthase, Phosphatidylinositol 3-Kinases, Nitric Oxide Donors, Hepatocytes, Mice, Nitric Oxide Synthase Type II
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